EFFECTS OF TANDOSPIRONE ON 2ND MESSENGER SYSTEMS AND NEUROTRANSMITTERRELEASE IN THE RAT-BRAIN

We studied the effects of tandospirone, a novel serotonin (5-HT)(1A) r eceptor-related anxiolytic, on the intracellular second messenger syst ems and neurotransmitter release. 2. Tandospirone inhibited forskolin- stimulated adenylate cyclase activity in rat hippocampal membranes by activation of 5-HT1A receptors and had high efficacy comparable to 5-H T1A receptor agonists such as 5-HT and 8-hydroxy-2-(di-n-propylamino)t etralin (8-OH-DPAT). 3. Tandospirone suppressed carbachol-stimulated p hosphatidyl-inositol metabolism (PI response), which was shown to be a 5-HT1A receptor-mediated event. 4. Tandospirone did not affect the re lease of 5-HT, norepinephrine (NE), dopamine (DA) and acetylcholine (A Ch) from rat brain slice preparations. 5. These findings suggested tha t tandospirone shows high agonistic efficacy on the postsynaptic 5-HT1 A receptors but does not affect the presynaptic autoreceptors located on nerve endings. The modulation of the second messenger system via po stsynaptic 5-HT1A receptors might be involved in the anxiolytic effica cy of tandospirone.